Abstract

A comparison has been made of the toxicity, the blood pressure effects, and the fate in the animal organism of l-nornicotine, l-nicotine, monomethyl nicotinium iodide, isomonomethyl nicotinium iodide and dimethyl nicotinium di-iodide.

The integrity of the pyridine nitrogen appears to be essential to the high degree of toxicity of nicotine and methylated and demethylated nicotines. On the other hand, progressive methylation of the pyrrolidine nitrogen increases the toxicity, as judged by intraperitoneal administration in white mice, in the ratio of 1:2:4, for nornicotine, nicotine, and monomethyl nicotinium iodide. The ratio of LD50 by intraperitoneal administration in mice to the LD50 by intravenous administration in rabbits is respectively 7.2, 1.6 and 11.6 for the three compounds. The difference in the dissociation constants of the three bases is offered as an explanation for this phenomenon.

The pressor effect on the anesthetized dog of nornicotine and monomethyl nicotinium iodide is respectively one-twelfth and two-thirds of that of a molecular equivalent of nicotine. Isomonomethyl nicotinium iodide and diemthyl nicotinium di-iodide in similar amounts have no effect and in doses of 100 times the threshold pressor dose of nicotine have a depressor effect.

In the dog, the course of metabolism of the methylated and demethylated derivatives of nicotine appears to be unlike that of nicotine. No evidence has been found to indicate that the detoxication of nicotine in the animal organism involves either methylation or demethylation of the molecule.